Sensor protein QseC (QseC) (QseC)

Sensor protein QseC is a membrane-bound histidine sensor kinase that serves as a critical component of the QseBC two-component signaling system in various Gram-negative bacteria, including Escherichia coli and Salmonella [1, 4]. It acts as a bacterial adrenergic receptor, integrating interkingdom signaling by sensing both the bacterial autoinducer-3 (AI-3) and host stress hormones like epinephrine and norepinephrine [6, 7]. Upon activation, QseC undergoes autophosphorylation and transfers the phosphate group to the response regulator QseB, which then coordinates the expression of virulence factors, motility genes, and biofilm formation [4, 15]. Because QseC is conserved across many pathogens and is essential for pathogenesis but not for bacterial growth, it has emerged as a promising target for anti-virulence therapies [1, 5]. Small molecule inhibitors like LED209 have been developed to allosterically modify QseC, effectively 'disarming' the bacteria without exerting the strong selective pressure for resistance typically seen with traditional antibiotics [1, 12]. This approach offers a novel strategy to combat multi-drug resistant infections by targeting the pathogen's ability to cause disease rather than its survival [3, 4]. Research has shown that QseC inhibition can attenuate virulence in animal models of infection, such as rabbit and mouse models, without causing toxicity to the host [1, 13]. Furthermore, QseC also possesses phosphatase activity that is necessary for dephosphorylating QseB to maintain proper regulation of gene expression [16, 17].

Other names

QseC histidine kinaseygiYBacterial adrenergic receptor

LED209 acts as a prodrug that allosterically modifies QseC to inhibit its autophosphorylation and subsequent activation of virulence genes; it also blocks the binding of host catecholamines and bacterial AI-3 signals [1, 2, 12].